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- Publisher Website: 10.1007/s12031-019-01287-y
- Scopus: eid_2-s2.0-85062990742
- PMID: 30874970
- WOS: WOS:000472082700018
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Article: Secretin Prevents Apoptosis in the Developing Cerebellum Through Bcl-2 and Bcl-xL
Title | Secretin Prevents Apoptosis in the Developing Cerebellum Through Bcl-2 and Bcl-xL |
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Authors | |
Keywords | Secretin Apoptosis Bcl-2 family proteins CREB PKA |
Issue Date | 2019 |
Publisher | Humana Press, Inc. The Journal's web site is located at http://www.springer.com/humana+press/neuroscience/journal/12031 |
Citation | Journal of Molecular Neuroscience, 2019, v. 68, p. 494-503 How to Cite? |
Abstract | Secretin (SCT) is involved in a variety of physiological processes and has been implicated in preventing apoptosis during brain development. However, little is known about the molecular mechanism underlying its neuroprotective effects. The B cell lymphoma 2 (Bcl-2) family proteins, such as Bcl-2 and Bcl-xL, determine the commitment of neurons to apoptosis. In SCT knockout mice, we found reduced transcript levels of anti-apoptotic genes Bcl-2 and Bcl-xL, but not of pro-apoptotic gene Bax, in the developing cerebellum. SCT treatment on ex vivo cultured cerebellar slices triggered a time-dependent increase of Bcl-2 and Bcl-xL expression. This SCT-induced transcriptional regulation of Bcl-2 and Bcl-xL was dependent on the cyclic AMP (cAMP) response element-binding protein (CREB), which is a key survival factor at the convergence of multiple signaling cascades. We further demonstrated that activation of CREB by SCT was mediated by cAMP/protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) cascades. These findings, collectively, provide an uncharacterized signaling cascade for SCT-mediated neuronal survival, in which SCT promotes the key anti-apoptotic elements Bcl-2 and Bcl-xL in the intrinsic death pathway through PKA- and ERK-regulated CREB phosphorylation. |
Persistent Identifier | http://hdl.handle.net/10722/273457 |
ISSN | 2023 Impact Factor: 2.8 2023 SCImago Journal Rankings: 0.747 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wang, L | - |
dc.contributor.author | Zhang, L | - |
dc.contributor.author | Chow, BKC | - |
dc.date.accessioned | 2019-08-06T09:29:20Z | - |
dc.date.available | 2019-08-06T09:29:20Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Journal of Molecular Neuroscience, 2019, v. 68, p. 494-503 | - |
dc.identifier.issn | 0895-8696 | - |
dc.identifier.uri | http://hdl.handle.net/10722/273457 | - |
dc.description.abstract | Secretin (SCT) is involved in a variety of physiological processes and has been implicated in preventing apoptosis during brain development. However, little is known about the molecular mechanism underlying its neuroprotective effects. The B cell lymphoma 2 (Bcl-2) family proteins, such as Bcl-2 and Bcl-xL, determine the commitment of neurons to apoptosis. In SCT knockout mice, we found reduced transcript levels of anti-apoptotic genes Bcl-2 and Bcl-xL, but not of pro-apoptotic gene Bax, in the developing cerebellum. SCT treatment on ex vivo cultured cerebellar slices triggered a time-dependent increase of Bcl-2 and Bcl-xL expression. This SCT-induced transcriptional regulation of Bcl-2 and Bcl-xL was dependent on the cyclic AMP (cAMP) response element-binding protein (CREB), which is a key survival factor at the convergence of multiple signaling cascades. We further demonstrated that activation of CREB by SCT was mediated by cAMP/protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) cascades. These findings, collectively, provide an uncharacterized signaling cascade for SCT-mediated neuronal survival, in which SCT promotes the key anti-apoptotic elements Bcl-2 and Bcl-xL in the intrinsic death pathway through PKA- and ERK-regulated CREB phosphorylation. | - |
dc.language | eng | - |
dc.publisher | Humana Press, Inc. The Journal's web site is located at http://www.springer.com/humana+press/neuroscience/journal/12031 | - |
dc.relation.ispartof | Journal of Molecular Neuroscience | - |
dc.rights | This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI] | - |
dc.subject | Secretin | - |
dc.subject | Apoptosis | - |
dc.subject | Bcl-2 family proteins | - |
dc.subject | CREB | - |
dc.subject | PKA | - |
dc.title | Secretin Prevents Apoptosis in the Developing Cerebellum Through Bcl-2 and Bcl-xL | - |
dc.type | Article | - |
dc.identifier.email | Chow, BKC: bkcc@hku.hk | - |
dc.identifier.authority | Chow, BKC=rp00681 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1007/s12031-019-01287-y | - |
dc.identifier.pmid | 30874970 | - |
dc.identifier.scopus | eid_2-s2.0-85062990742 | - |
dc.identifier.hkuros | 299869 | - |
dc.identifier.volume | 68 | - |
dc.identifier.spage | 494 | - |
dc.identifier.epage | 503 | - |
dc.identifier.isi | WOS:000472082700018 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0895-8696 | - |